RU2466994C2 - 7-membered cyclic compounds, methods of their obtaining and their pharmaceutical application - Google Patents

7-membered cyclic compounds, methods of their obtaining and their pharmaceutical application Download PDF

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RU2466994C2
RU2466994C2 RU2008152044/04A RU2008152044A RU2466994C2 RU 2466994 C2 RU2466994 C2 RU 2466994C2 RU 2008152044/04 A RU2008152044/04 A RU 2008152044/04A RU 2008152044 A RU2008152044 A RU 2008152044A RU 2466994 C2 RU2466994 C2 RU 2466994C2
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formula
alkyl
compound
alkoxy
iii
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RU2008152044/04A
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RU2008152044A (en
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Цуёси МУТО (JP)
Цуёси МУТО
Таисаку ТАНАКА (JP)
Таисаку ТАНАКА
Хироси МАРУОКА (JP)
Хироси МАРУОКА
Сеиити ИМАДЗО (JP)
Сеиити ИМАДЗО
Ёсиаки ТОМИМОРИ (JP)
Ёсиаки ТОМИМОРИ
Кодзи САТО (JP)
Кодзи САТО
Цутоми ЯГИ (JP)
Цутоми ЯГИ
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Дайити Санкё Компани, Лимитед
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Abstract

FIELD: chemistry.
SUBSTANCE: described is method of obtaining 7-membered heterocyclic compounds of formula
Figure 00000299
(R-Ia) and
Figure 00000300
(S-Ia), where values of radical are given in formula of the invention, basing on compound
Figure 00000301
(Vaa) via corresponding isocyanate derivative and interaction of the latter with corresponding diazepin reagent.
EFFECT: target compounds possess inhibiting activity with respect to chymase.
2 cl, 331 ex, 12 tbl

Description

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Claims (2)

1. Способ получения соединения формулы (R-Ia) или (S-Ia)
Figure 00000288

Figure 00000289

где R2 и R3 независимо представляют собой (1) водород, (2) галоген или (3) C1-С6алкил;
R5 и R6 независимо представляют собой (1) водород или (2) C1-С6алкил необязательно замещенный группой, выбранной из группы, состоящей из (i) карбоксила, (ii) C1-С6алкокси, (iii) C1-С6алкоксикарбонила, (iv) C6-С12арилоксикарбонила, (v) С1-С10 гетероарилоксикарбонила и (vi) амино;
R2 и R3, а также R5 и R6 независимо могут образовывать 3-8-членное кольцо;
Ar' представляет собой (С6-С14) ароматическую углеводородную группу, которая может быть замещена 1-5 группами, выбранными из группы, состоящей из (i) атомов галогена, (ii) нитро, (iii) циано, (iv) (С1-С6)-алкила, который может быть, необязательно, замещен 1-3 атомами галогена, и (v) (С1-С6)-алкокси, который может быть необязательно замещен 1-3 атомами галогена,
Ха представляет собой линейный или разветвленный (С1-С6)-алкилен,
R7a представляет собой (С1-С6)-алкил, который может быть необязательно замещен группой, выбранной из группы, состоящей (i) карбоксила, (ii) (C1-С6)-алкоксикарбонила, (iii) фенила, (iv) гидроксила, (v) (С1-С6)-алкокси и (vi) атома галогена;
R8a представляет собой атом водорода;
R26, R27 и R28 могут быть одинаковыми или разными и обозначают (i) атом водорода, (ii) атом галогена, (iii) циано, (iv) нитро, (v) (С1-С6)-алкил, (vi) (С1-С6)-алкокси, (vii) (С1-С6)-алкоксикарбонил, (viii) (C1-С6)-алкилсульфонил, (ix) карбоксил, (х) карбокси-(С1-С6)-алкил, (xi) гидроксил или (xii) амино,
или его соли, или сольвата,
включающий:
превращение соединения формулы (Vaa)
Figure 00000290

где R7a и R8a имеют значения, указанные выше, a R26a, R27a и R28a могут быть одинаковыми или разными и обозначают (i) атом водорода, (ii) атом галогена, (iii) циано, (iv) нитро, (v) (С1-С6)-алкил, (vi) (С1-С6)-алкокси, (vii) (С1-С6)-алкоксикарбонил, (viii) (С1-С6)-алкилсульфонил, (ix) карбоксил, защищенный трет-бутилом, бензилом или 4-метоксибензилом, (х) карбокси-(С1-С6)-алкил, защищенный трет-бутилом, бензилом или 4-метоксибензилом, или (xi) гидроксил, защищенный трет-бутилом, бензилом или 4-метоксибензилом, или его соли
в соединение формулы (1Ха)
Figure 00000291

где R7a, R8a, R26a, R27a и R28a имеют значения, указанные выше,
последующую реакцию сочетания полученного соединения формулы (1Ха) и соединения формулы (R-IIIa) или (S-IIIa)
Figure 00000292

Figure 00000293

где Ar', Ха, R2, R3, R5 и R6 имеют значения, указанные выше, а Ра обозначает бензил, 4-метоксибензил, 2,4-диметоксибензил или 2,4,6-триметоксибензил,
которая дает соединение формулы (R-Ib) или формулы (S-Ib):
Figure 00000294

Figure 00000295

где Ar', Ха, R2, R3, R5, R6, R7a, R8a, R26a, R27a, R28a и Ра имеют значения, указанные выше,
и удаление Pa из полученного соединения формулы (R-Ib) или формулы (S-Ib) и необязательное восстановление и/или гидролиз полученного соединения одновременно с удалением Ра, или перед удалением Ра, и/или после удаления Ра в случае, когда R26a, R27a или R28a полученного соединения имеют защитную группу, или в случае, когда R26a, R27a или R28a полученного соединения представляют собой нитро, и R26, R27 или R28 этих соединений, имеющих формулу (R-Ia) или (S-Ia), представляют собой амино.1. The method of obtaining the compounds of formula (R-Ia) or (S-Ia)
Figure 00000288

Figure 00000289

where R 2 and R 3 independently represent (1) hydrogen, (2) halogen or (3) C 1 -C 6 alkyl;
R 5 and R 6 independently represent (1) hydrogen or (2) C 1 -C 6 alkyl optionally substituted with a group selected from the group consisting of (i) carboxyl, (ii) C 1 -C 6 alkoxy, (iii) C 1 -C 6 alkoxycarbonyl, (iv) C 6 -C 12 aryloxycarbonyl, (v) C 1 -C 10 heteroaryloxycarbonyl and (vi) amino;
R 2 and R 3 , as well as R 5 and R 6 independently can form a 3-8 membered ring;
Ar 'is a (C 6 -C 14 ) aromatic hydrocarbon group which may be substituted with 1-5 groups selected from the group consisting of (i) halogen atoms, (ii) nitro, (iii) cyano, (iv) ( C 1 -C 6 ) -alkyl, which may optionally be substituted by 1-3 halogen atoms, and (v) (C 1 -C 6 ) -alkoxy, which may optionally be substituted by 1-3 halogen atoms,
Xa is a linear or branched (C 1 -C 6 ) -alkylene,
R 7a represents (C 1 -C 6 ) -alkyl, which may be optionally substituted with a group selected from the group consisting of (i) carboxyl, (ii) (C 1 -C 6 ) -alkoxycarbonyl, (iii) phenyl, ( iv) hydroxyl, (v) (C 1 -C 6 ) alkoxy and (vi) halogen atom;
R 8a represents a hydrogen atom;
R 26 , R 27 and R 28 may be the same or different and represent (i) a hydrogen atom, (ii) a halogen atom, (iii) cyano, (iv) nitro, (v) (C 1 -C 6 ) -alkyl, (vi) (C 1 -C 6 ) alkoxy, (vii) (C 1 -C 6 ) alkoxycarbonyl, (viii) (C 1 -C 6 ) alkylsulfonyl, (ix) carboxyl, (x) carboxy- ( C 1 -C 6 ) -alkyl, (xi) hydroxyl or (xii) amino,
or its salt, or MES,
including:
conversion of a compound of formula (Vaa)
Figure 00000290

where R 7a and R 8a have the meanings indicated above, a R 26a , R 27a and R 28a may be the same or different and represent (i) a hydrogen atom, (ii) a halogen atom, (iii) cyano, (iv) nitro, (v) (C 1 -C 6 ) -alkyl, (vi) (C 1 -C 6 ) -alkoxy, (vii) (C 1 -C 6 ) -alkoxycarbonyl, (viii) (C 1 -C 6 ) - alkylsulfonyl, (ix) carboxyl protected by tert-butyl, benzyl or 4-methoxybenzyl, (x) carboxy- (C 1 -C 6 ) -alkyl protected by tert-butyl, benzyl or 4-methoxybenzyl, or (xi) hydroxyl, protected by tert-butyl, benzyl or 4-methoxybenzyl, or a salt thereof
to the compound of formula (1Xa)
Figure 00000291

where R 7a , R 8a , R 26a , R 27a and R 28a have the meanings indicated above,
a subsequent coupling reaction of the obtained compound of formula (1Xa) and a compound of formula (R-IIIa) or (S-IIIa)
Figure 00000292

Figure 00000293

where Ar ', Xa, R 2 , R 3 , R 5 and R 6 are as defined above, and Ra is benzyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl or 2,4,6-trimethoxybenzyl,
which gives a compound of formula (R-Ib) or formula (S-Ib):
Figure 00000294

Figure 00000295

where Ar ', Xa, R 2 , R 3 , R 5 , R 6 , R 7a , R 8a , R 26a , R 27a , R 28a and Pa are as defined above,
and removing Pa from the resulting compound of formula (R-Ib) or formula (S-Ib) and optionally reducing and / or hydrolyzing the resulting compound simultaneously with the removal of Pa, or before the removal of Pa, and / or after the removal of Pa in the case where R 26a , R 27a or R 28a of the obtained compound have a protective group, or in the case when R 26a , R 27a or R 28a of the obtained compound are nitro, and R 26 , R 27 or R 28 of these compounds having the formula (R-Ia) or (S-Ia) are amino. 2. Способ по п.1, где Ar' представляет собой фенил, который необязательно замещен 1-5 группами, выбранными из (i) атома галогена, (ii) нитро, (iii) циано, (iv) C1-С6алкила, который необязательно замещен 1-3 атомами галогена, и (v) C1-С6алкокси, который необязательно замещен 1-3 атомами галогена, и R2, R3, R5 и R6 все являются водородом. 2. The method according to claim 1, where Ar 'represents phenyl, which is optionally substituted by 1-5 groups selected from (i) a halogen atom, (ii) nitro, (iii) cyano, (iv) C 1 -C 6 alkyl which is optionally substituted by 1-3 halogen atoms, and (v) C 1 -C 6 alkoxy, which is optionally substituted by 1-3 halogen atoms, and R 2 , R 3 , R 5 and R 6 are all hydrogen.
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Families Citing this family (13)

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KR101256334B1 (en) * 2006-10-18 2013-04-18 이데미쓰 고산 가부시키가이샤 Polycarbonate copolymer, method for producing the same, molded body, optical material, and electrophotographic photosensitive body
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GB0912778D0 (en) 2009-07-22 2009-08-26 Eisai London Res Lab Ltd Fused aminodihydro-oxazine derivatives
GB0912777D0 (en) 2009-07-22 2009-08-26 Eisai London Res Lab Ltd Fused aminodihydropyrimidone derivatives
NZ600748A (en) * 2009-12-25 2014-06-27 Daiichi Sankyo Co Ltd Seven-membered ring compound and pharmaceutical use therefor
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BR112013016241A2 (en) 2011-01-21 2016-07-12 Eisai R&D Man Co Ltd compound, and method for making a compound
GB201101139D0 (en) 2011-01-21 2011-03-09 Eisai Ltd Fused aminodihydrothiazine derivatives
GB201101140D0 (en) 2011-01-21 2011-03-09 Eisai Ltd Fused aminodihydrothiazine derivatives
CN103601675B (en) * 2013-10-08 2015-10-28 南京复兴生物科技有限公司 A kind of preparation method of 5-aminomethyl nicotinic acid
CN103622024B (en) * 2013-12-13 2016-05-18 泸州百草堂健康产品有限公司 A kind of food, health products or pharmaceutical composition with relieve sore throat effect and its production and use
CN111018864A (en) * 2019-12-24 2020-04-17 温州大学新材料与产业技术研究院 Preparation method of indole-fused octamer lactam compound

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU403677A1 (en) * 1970-10-01 1973-10-26
RU2301803C2 (en) * 2002-10-18 2007-06-27 Мерк Энд Ко., Инк. Derivatives of hexahydrodiazepinone, pharmaceutical composition containing thereof and using in preparing medicinal agent for treatment of non-insulin dependent diabetes mellitus

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2257171A1 (en) 1972-11-22 1974-05-30 Boehringer Sohn Ingelheim 4-Acyl-1,4-benzodiazepine-2,5-diones - with anticonvulsant activity prepd byacylation of 4-unsubst. cpds
KR20010089168A (en) * 1998-08-21 2001-09-29 도리이 신이치로 Quinazoline derivatives and pharmaceutical applications thereof
JP2000247908A (en) 1999-03-01 2000-09-12 Welfide Corp Itching inhibitor
DE60034545T2 (en) 1999-11-01 2007-10-25 Asubio Pharma Co., Ltd. USE OF CHYMASE INHIBITORS AGAINST VASCULAR LIPID DEPOSITION
CN1366461A (en) 2000-02-22 2002-08-28 三得利株式会社 Preventive or therapeutic drugs for dermatitises containing chymase inhibitors as active ingredient
CA2365606A1 (en) 2000-02-22 2001-08-30 Suntory Limited Medicament for prevention or treatment of various diseases involving an increase in eosinophils chymase inhibitor as effective ingredient
CA2368382A1 (en) 2000-02-22 2001-08-30 Suntory Limited Medicament for prevention and treatment of dermatitis having chymase inhibitor as effective ingredient
US20040019068A1 (en) 2000-10-19 2004-01-29 Mizuo Miyazaki Novel remedies or preventives for angiostenosis
US6919365B2 (en) 2001-04-11 2005-07-19 Senju Pharmaceutical Co., Ltd. Imidazolidinedione derivatives and use thereof as drugs
WO2003007964A1 (en) 2001-07-18 2003-01-30 Nippon Kayaku Kabushiki Kaisha Remedial or preventive agent for cardiopathy or aneurysm containing chymase inhibitory compound
KR101011175B1 (en) 2001-10-19 2011-01-26 오르토-맥네일 파마슈티칼, 인코퍼레이티드 Phosphonic acid compounds as serine proteases
CN1435408A (en) * 2002-02-01 2003-08-13 中国科学院化学研究所 Process of one-step hydrogenation synthesis of alpha-substd. beta-amino acid
CA2479353C (en) 2002-03-15 2010-09-14 Toa Eiyo Ltd. N-substituted benzothiophenesulfonamide derivative
JP2003342265A (en) 2002-05-22 2003-12-03 Senju Pharmaceut Co Ltd Triazolidine derivative and its pharmaceutical use
WO2004007464A1 (en) 2002-07-10 2004-01-22 Sumitomo Pharmaceuticals Co., Ltd. Imidazole derivative
JP2004067584A (en) 2002-08-06 2004-03-04 Sumitomo Pharmaceut Co Ltd New pyridone derivative
JP4427266B2 (en) 2003-03-28 2010-03-03 第一ファインケミカル株式会社 β-alanine derivative and method for producing the same
EP1640369A4 (en) 2003-06-27 2007-10-31 Dainippon Sumitomo Pharma Co Thiazolimine compound and oxazolimine compound
ES2441206T3 (en) * 2003-09-03 2014-02-03 Raqualia Pharma Inc. Phenyl or pyridylamide compounds as prostaglandin E2 antagonists
RU2006121990A (en) 2003-11-21 2007-12-27 Эррэй Биофарма Инк. (Us) ACT PROTEINKINASE INHIBITORS
ATE493421T1 (en) 2004-01-23 2011-01-15 Janssen Pharmaceutica Nv NEW INHIBITORS OF CHYMASE
CN1946391A (en) * 2004-04-20 2007-04-11 辉瑞产品公司 Combinations comprising alpha-2-delta ligands
CA2589638C (en) * 2004-12-02 2014-05-20 Asubio Pharma Co., Ltd. 7-membered ring compound and method of production and pharmaceutical application thereof
WO2006120544A1 (en) * 2005-05-06 2006-11-16 Pfizer Limited β-AMINO ACID DERIVATIVES

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU403677A1 (en) * 1970-10-01 1973-10-26
RU2301803C2 (en) * 2002-10-18 2007-06-27 Мерк Энд Ко., Инк. Derivatives of hexahydrodiazepinone, pharmaceutical composition containing thereof and using in preparing medicinal agent for treatment of non-insulin dependent diabetes mellitus

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GATES M. et. al JOURNAL OF ORGANIC CHEMISTRY, 1980, v.45, №9, p.1675-1681. *

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